Acetic Acid → (S)-5-(3-aminopropyl)-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione hydrochloride

HRID 854707Notes

Reaction equation

HRID 854707 reaction equation
[ClH:1].[F:2][C:3]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][C@H:7]([NH2:14])[CH2:8]2.[Si](O[CH2:23][C:24](=O)[CH2:25][CH2:26][CH2:27][N:28]1C(=O)C2C(=CC=CC=2)C1=O)(C(C)(C)C)(C)C.[S-:40][C:41]#[N:42].[K+].C(O)(=O)C.[BH4-].[Na+]>C(OCC)(=O)C.O>[ClH:1].[NH2:28][CH2:27][CH2:26][CH2:25][C:24]1[N:14]([C@H:7]2[CH2:6][CH2:5][C:4]3[C:9](=[CH:10][C:11]([F:13])=[CH:12][C:3]=3[F:2])[CH2:8]2)[C:41](=[S:40])[NH:42][CH:23]=1

Participants

8

Reactant 5

HCID 176Acetic Acid2×HCID 516872Potassium thiocyanateHCID 4311764Sodium borohydrideHCID 116029612-[5-(tert-Butyldimethylsilanyloxy)4-oxopentyl]isoindole-1,3-dioneHCID 66789737(S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Product 1

HCID 11674895(S)-5-(3-aminopropyl)-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A stirred mixture of (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl amine hydrochloride (0.22 g, 1.0 mmol), 2-[5-(tert-butyldimethylsilanyloxy)-4-oxopentyl]isoindole-1, 3-dione (0.38 g, 1.05 mmol), potassium thiocyanate (0.11 g, 1.10 mmol), water (0.18 g, 1.0 mmol) and acetic acid (0.3 mL, 5.0 mmol) in ethyl acetate (3 mL) was refluxed for 7 hours, cooled to room temperature, washed by sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica using ethyl acetate—petroleum ether mixture as eluent. The resulting oil (0.18 g) was dissolved in a mixture of isopropanol (5 mL) and THF (2 mL). Water (0.8 mL) and sodium borohydride (0.066 g, 1.74 mmol) were added at room temperature and the mixture was stirred for 1.5 hours. Acetic acid (0.6 ml, 10 mmol) was added and the solution was refluxed for two hours then evaporated in vacuo to dryness. The residue was taken up into acetone, the solid was filtered off, and the filtrate was acidified with 2N HCl solution in ethyl acetate. The precipitate was collected and washed with acetone to afford crystals, which decomposed without melting.

Workup

  1. temperaturewas refluxed for 7 hours
  2. washwashed by sodium bicarbonate solution
  3. dry with materialdried over anhydrous magnesium sulphate
  4. customevaporated in vacuo
  5. customThe residue was purified by column chromatography on silica
  6. dissolutionThe resulting oil (0.18 g) was dissolved in a mixture of isopropanol (5 mL) and THF (2 mL)
  7. temperaturethe solution was refluxed for two hours
  8. customthen evaporated in vacuo to dryness
  9. filtrationthe solid was filtered off
  10. customThe precipitate was collected
  11. washwashed with acetone
  12. customto afford crystals, which

Sources & evidence

ORD record
ord-ac3485bb24f04c258a74d20c9690df54
Source dataset
uspto-grants-2007_08
Patent number
US07259271B2

Reaction notes

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